Elizabeth A Jensen1,2, Jonathan A Young3,4, Jaycie Kuhn3,5, Maria Onusko6,5, Joshua Busken3, Edward O List1,3,6, John J Kopchick1,3,6,4, Darlene E Berryman7,8,9,10,11. 1. Translational Biomedical Sciences Program, Graduate College, Ohio University, Athens, OH, USA. 2. Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA. 3. Edison Biotechnology Institute, Ohio University, Athens, OH, USA. 4. Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA. 5. College of Arts and Sciences, Ohio University, Athens, OH, USA. 6. The Diabetes Institute, Ohio University, Parks Hall Suite 142, Athens, OH, USA. 7. Translational Biomedical Sciences Program, Graduate College, Ohio University, Athens, OH, USA. berrymad@ohio.edu. 8. Edison Biotechnology Institute, Ohio University, Athens, OH, USA. berrymad@ohio.edu. 9. The Diabetes Institute, Ohio University, Parks Hall Suite 142, Athens, OH, USA. berrymad@ohio.edu. 10. Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA. berrymad@ohio.edu. 11. Office of Research and Grants, Heritage College of Osteopathic Medicine, Ohio University, Irvine Hall 220B, Athens, OH, 45701, USA. berrymad@ohio.edu.
Abstract
PURPOSE: Growth hormone (GH) has an important role in intestinal barrier function, and abnormalities in GH action have been associated with intestinal complications. Yet, the impact of altered GH on intestinal gross anatomy and morphology remains unclear. METHODS: This study investigated the influence of GH signaling on gross anatomy, morphology, and fibrosis by characterizing the small and large intestines in male and female bovine growth hormone transgenic (bGH) mice and GH receptor gene-disrupted (GHR-/-) mice at multiple timepoints. RESULTS: The length, weight, and circumference of the small and large intestines were increased in bGH mice and decreased in GHR-/- mice across all ages. Colon circumference was significantly increased in bGH mice in a sex-dependent manner while significantly decreased in male GHR-/- mice. Villus height, crypt depth, and muscle thickness of the small intestine were generally increased in bGH mice and decreased in GHR-/- mice compared to controls with age- and sex-dependent exceptions. Colonic crypt depth and muscle thickness in bGH and GHR-/- mice were significantly altered in an age- and sex-dependent manner. Fibrosis was increased in the small intestine of bGH males at 4 months of age, but no significant differences were seen between genotypes at other timepoints. CONCLUSION: This study observed notable opposing findings in the intestinal phenotype between mouse lines with GH action positively associated with intestinal gross anatomy (i.e. length, weight, and circumference). Moreover, GH action appears to alter morphology of the small and large intestines in an age- and sex-dependent manner.
PURPOSE: Growth hormone (GH) has an important role in intestinal barrier function, and abnormalities in GH action have been associated with intestinal complications. Yet, the impact of altered GH on intestinal gross anatomy and morphology remains unclear. METHODS: This study investigated the influence of GH signaling on gross anatomy, morphology, and fibrosis by characterizing the small and large intestines in male and female bovine growth hormone transgenic (bGH) mice and GH receptor gene-disrupted (GHR-/-) mice at multiple timepoints. RESULTS: The length, weight, and circumference of the small and large intestines were increased in bGH mice and decreased in GHR-/- mice across all ages. Colon circumference was significantly increased in bGH mice in a sex-dependent manner while significantly decreased in male GHR-/- mice. Villus height, crypt depth, and muscle thickness of the small intestine were generally increased in bGH mice and decreased in GHR-/- mice compared to controls with age- and sex-dependent exceptions. Colonic crypt depth and muscle thickness in bGH and GHR-/- mice were significantly altered in an age- and sex-dependent manner. Fibrosis was increased in the small intestine of bGH males at 4 months of age, but no significant differences were seen between genotypes at other timepoints. CONCLUSION: This study observed notable opposing findings in the intestinal phenotype between mouse lines with GH action positively associated with intestinal gross anatomy (i.e. length, weight, and circumference). Moreover, GH action appears to alter morphology of the small and large intestines in an age- and sex-dependent manner.
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